More than a thousand people are expected to turn up to the park on Friday to "peacefully" protest and call on the Government to legalise the Class B drug.
The rally takes place every year on April 20 with marijuana lovers set to gather to demand the drug is decriminalised.
On the Facebook page for the event, 1,300 have already pledged to attend. A large police presence is expected.
In 2015, the pro-Cannabis rally saw more than 50 people arrested, despite claims from organisers that the event was peaceful.
Last year, 12 people were detained by police at the rally.
Police said that officers will be present and that the usual drug laws will apply on the day. Random police searches are expected.
A spokesman said: “We are aware of a planned event due to be held in Hyde Park at 12.00hrs on Friday, 20 April.
“A proportionate policing plan will be in place.
“Legislation under the Misuse of Drugs Act 1971 will be enforced as it would be under normal police conditions during this event.”
The origin of 420 is subject to numerous urban myths and theories.
It has been suggested that the number 420 came from the penal code the Californian police used to categorise cannabis cases.
In 1971, students at a Californian high school allegedly organised to meeting at 4.20pm to find a plot of land to plant a cannabis plant.
Rallies and celebrations of weed are set to take place across the world today, stretching as far as New Zealand and America.
Tony Blair’s Labour government announced it would be changing the classification of the drug to C in 2001, hoping that the move would enable officers to concentrate on more serious drug offences.
But he backtracked following the 2005 General Election, believing the move sent out the “wrong message”.
Cannabis users can go to jail if caught, though traffickers and dealers are more likely to receive prison sentences.